系統識別號 U0026-0812200914381987
論文名稱(中文) 研究褪黑激素及牛磺酸對敗血症大鼠之氧化壓力和出血性潰瘍的作用
論文名稱(英文) Effect of taurine or melatonin on gastric oxidative stress and hemorrhagic ulcer in septic rats
校院名稱 成功大學
系所名稱(中) 藥理學研究所
系所名稱(英) Department of Pharmacology
學年度 96
學期 2
出版年 97
研究生(中文) 周瑞怡
研究生(英文) Jui-yi Chou
電子信箱 s2693102@mail.ncku.edu.tw
學號 s2693102
學位類別 碩士
語文別 中文
論文頁數 98頁
口試委員 指導教授-洪正路
中文關鍵字 牛磺酸  褪黑激素 
英文關鍵字 septic rats  gastric hemorrhagic ulcer 
中文摘要 敗血症是指因感染所引起之全身性發炎反應,儘管過去幾十年來醫學上有顯著的進步,但敗血症的致死率至今仍是居高不下,臨床上產生敗血症的病人中,以肺部感染為最多,腹腔感染則次之,而在敗血症關於胃潰瘍方面的研究更是相當不足。牛磺酸為膽汁及飲食中常見之胺基酸,褪黑激素是腦部松果體所分泌的一種激素,文獻指出均具有抗氧化的作用。因此本實驗以腹腔注射10 mg/kg格蘭氏陰性菌外膜的脂多醣 (lipopolysaccharide, LPS)誘發大鼠產生敗血症,於0、24小時抽血測量白血球數量,血糖值及體溫的改變,並於第21小時執行外科手術以人工胃液灌流三小時後,取出胃黏膜作各種參數分析,包括潰瘍面積、胃酸逆擴散之測定、血紅素含量、組織胺濃度、黏液產量、麩胺基硫(glutathione, GSH)、脂質過氧化(lipid peroxidation, LPO)、過氧化氫酶(catalase, CAT)、超氧化物岐化酶(superoxide dismutase, SOD)、穀胱甘肽過還原酶(glutathione reductase, GSH Rd)、穀胱甘肽過氧化酶(glutathione peroxidase, GSH Px)及脊椎過氧化酵素(myeloperoxidase, MPO),以評估氧化性壓力及嗜中性球浸潤的程度,並探討牛磺酸與褪黑激素對敗血症之療效及可能機轉。結果發現牛磺酸與褪黑激素可能經由減少潰瘍面積、血紅素含量,增加黏液產量、麩胺基硫含量而有胃部保護作用,降低LPS所引起敗血症動物的死亡率。
英文摘要 Sepsis is the systemic inflammatory response to infection. In spite of marked advance in medicine, the mortality rates in septic patients are still rising. Sepsis can cause failures of multiple organs, including heart, lung, liver, kidney and gastrointestinal system. Global tissue hypoxia results in an imbalance between systemic oxygen delivery and demand, and is a key development of preceding multiple organ failure and death. Nevertheless, the mechanisms of gastric hemorrhagic ulcer in sepsis are unknown. Taurine is one of the most abundant amino acids in the body. Melatonin is secreted by the pineal gland. Both taurine and melatonin possess potential antioxidant effects. Whether these two drugs can ameliorate gastric hemorrhagic ulcer in septic rats is unknown. Intraperitoneal lipopolysaccharide (LPS; 10 mg/kg) was challenged to rats for 24 hours to induce sepsis. Animals were divided into four groups: (1) Sham operation (Sham) (2) Sham + melatonin (10、20、50 mg/kg); Sham + taurine (50、100、250 mg/kg) (3) LPS (4) LPS + melatonin; LPS + taurine. After gastric surgery, the rat stomachs were then irrigated for three hours with simulated gastric juice, and then to evaluate effects of melatonin and taurine on LPS-induced septic rats. At 0 and 24 hr after LPS treatment, the changes of white blood cell count, blood sugar, rectal temperature, gastric ulcerogenic factors (gastric acid back diffusion, histamine concentration, lipid peroxidation), gastric defensive parameters (gastric mucus and glutathione production in gastric mucosa), antioxidant effects (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase) were examined. The results showed that LPS produced severe gastric hemorrhagic ulcer and exacerbation of offensive factors while defensive parameters were decreased. These beneficial effects of melatonin and taurine may be attributed to reducing organ O2- levels and increasing activation of antioxidant enzymes (catalase, superoxide dismutase, glutathione reductase and glutathione peroxidase), thereby decreasing the mortality rates in LPS-induced septic rats.
論文目次 中文摘要………………………………………………………………Ι
第一章 緒論………………………………………………………… 1
第二章 實驗材料和方法…………………………………………… 19
第三章 實驗結果…………………………………………………… 41
第四章 討論………………………………………………………… 47
第五章 結論………………………………………………………… 58
參考文獻 1. Adamek RJ, Freitag M, Opferkuch W, Ruhl GH and Wegener M. Intravenous omeprazole/amoxillin and omeprazole pretreatment in Helicobacter pylori-positive acute peptic ulcer bleeding. A pilot study. Scand. J. Gastroenterol. (1994) 29: 880-883
2. Alberti C, Brun-Buisson C, Burchardi H, Martin C, Goodman S, Artigas A, Sicignano A, Palazzo M, Moreno R, and Boulme R. Epidemiology of sepsis and infection in ICU patients from an international multicentre cohort study. Intensive Care Med. (2002) 28: 108-121
3. Angus DC, Linde-Zwirble WT, Lidicker J, Clermont G, Carcillo J and Pinsky MR. Epidemiology of severe sepsis in the United States: analysis of incidence, outcome, and associated costs of care. Crit Care Med. (2001) 29: 1303-1310
4. Astiz ME and Rackow EC. Septic shock. Lancet. (1998) 351: 1501-1505
5. Bandyopadhyay D, Ghosh G, Bandyopadhyay A, and Reiter R J. Melatonin protects against piroxicam-induced gastric ulceration. J Pineal Res. (2004) 36: 195-203
6. Balkan J, Dorgu-Abbasoglu S, Kanbagli O, Cevikbas U, Aykac-Toker G and Uysal M. Taurine has a protective effect against thioacetamide-induced cirrhosis by decreasing oxidative stress. Human Exp. Toxicol. (2001) 20: 251-254
7. Ball HA, Cook JA, Wise WC and Halushka PV. Role of thromboxane, prostaglandins and leukotrienes in endotoxic and septic shock. Intensive Care Med. (1986) 12: 116-126
8. Barron RL. Pathophysiology of septic shock and implications for 108 therapy. Clin Pharm. (1993) 12: 829-845
9. Beal AL and Cerra FB. Multiple organ failure syndrome in the 1990s. Systemic inflammatory response and organ dysfunction. Jama. (1994) 271: 226-233
10. Beutler B, Milsark IW and Cerami AC. Passive immunization against cachectin/tumor necrosis factor protects mice from lethal effect of endotoxin. Science (1985) 229: 869-871
11. Body SC, Sasame HA and Body MR. High concentrations of glutathione in glandular stomach: possible implications for carcinogenesis. Science (1979) 205: 1010-1012
12. Bone RC, Balk RA, Cerra FB, Dellinger RP, Fein AM, Knaus WA, Schein RM and Sibbald WJ. Definitions for sepsis and organ failure and guidelines for the use of innovative therapies in sepsis. The ACCP/SCCM Consensus Conference Committee. American College of Chest Physicians/Society of Critical Care Medicine. Chest. (1992) 101: 1644-1655
13. Bone RC, Grodzin CJ and Balk RA. Sepsis: a new hypothesis for pathogenesis of the disease process. Chest. (1997) 112: 235-243
14. Borden CW and Hall WH. Fatal transfusion reactions from massive bacterial contamination of blood. N Engl J Med. (1951) 245: 760-765
15. Bosch MA, Garcia R, Pagani R, Portoles MT, Diaz-Laviada I, Abarca S, Ainaga MJ, Risco C and Municio AM. Induction of reversible shock by Escherichia coli lipopolysaccharide in rats. Changes in serum and cell membrane parameters. Br J Exp Pathol. (1988) 69: 805-812
16. Brandes RP, Koddenberg G, Gwinner W, Kim D, Kruse HJ, Busse R and Mugge A. Role of increased production of superoxide anions by NAD(P)H oxidase and xanthine oxidase in prolonged endotoxemia. Hypertension. (1999) 33: 1243-1249
17. Cadet J, Delatour T, Douki T, Gasparutto D, Pouget JP, Ravanat JL and Sauvaigo S. Hydroxyl radicals and DNA base damage. Mutat. Res. (1999) 424: 9-21
18. Canas P.E. The role of taurine and its derivatives on cellular hypoxia: a physiological view. Acta. Physiol. Pharmacol. Therap. Latinoam. (1992) 42: 133-137
19. Cannon JG, Tompkins RG, Gelfand JA, Michie HR, Stanford GG, van der Meer JW, Endres S, Lonnemann G, Corsetti J, Chernow B. Circulating interleukin-1 and tumor necrosis factor in septic shock and experimental endotoxin fever. J Infect Dis. (1990) 161: 79-84
20. Catto-Smith AG, Patrick MK, Scott RB, Davison JS and Gall DG. Gastric response to mucosal IgE-mediated reactions. Am. J. Physiol. (1989) 257: G704-G708
21. Cerra FB. Hypermetabolism-organ failure syndrome: a metabolic response to injury. Crit Care Clin. (1989) 5: 289-302
22. Chen SH and Pan S. Sources of superoxide radicals involved in the pathogenesis of diethyldithiocarbamate-induced gastric antral ulcer in rats. J. Formos. Med. Assoc. (1998) 97: 131-134
23. Chung RS, Field M and Silen W. Permeability of gastric mucosa to hydrogen and lithium. Gastroenterology. (1973) 64: 593-598
24. Corne SJ, Morrissey SM and Woods RJ. Proceedings, A method for the quantitative estimation of gastric barrier mucus. Am. J. Physiol. (1974) 242: 116-117
25. Chabot F, Mitchell JA, Gutteridge JM and Evans TW. Reactive oxygen species in acute lung injury. Eur Respir J. (1998) 11: 745-757
26. Curtis G.H. and Gall D.G. Macromolecular transport by rat gastric mucosa. Am. J. Physiol. (1992) 262: G1033-G1040
27. Das D, Bandyopadhyay D, Bhattacharjee M and Banerjee RK. Hydroxyl radical is the major causative factor in stress-induced gastric ulceration. Free Radic. Biol. Med. (1997) 23: 8-18
28. Davenport HW. Gastric mucosal hemorrhage in dogs. Effects of acid, aspirin and alcohol. Gastroenterology (1969) 56: 439-449
29. Deitch EA, Xu D, Franko L, Ayala A and Chaudry IH. Evidence favoring the role of the gut as a cytokine-generating organ in rats subjected to hemorrhagic shock. Shock. (1994) 1: 141-145
30. Dellinger RP, Carlet JM, Masur H, Gerlach H, Calandra T, Cohen J, Gea-Banacloche J, Keh D, Marshall JC, Parker MM. Surviving Sepsis Campaign guidelines for management of severe sepsis and septic shock. Crit Care Med. (2004) 32: 858-873
31. Dorinsky PM and Gadek JE. Mechanisms of multiple nonpulmonary organ failure in ARDS. Chest. (1989) 96: 885-892
32. de Vries I, van Deventer SJ, Debets J, Buller HR, ten Cate JW, Pauw W, Statius van Eps LW and Sturk A. Endotoxin-induced cytokines in human septicemia. Adv Exp Med Biol. (1990) 256: 635-640
33. Gannon B, Browning J, O’Brien P, Rogers P. Mucosal microvascular architecture of the fundus and body of human stomach. Gastroenterology (1984) 31: 866-875
34. Fink MP, Antosson JB, Wang H. Etiology of increased intestinal permeability in endotoxic pigs. Limited role for mesenteric hypoperfusion. Arch. Surg. (1991) 126: 231-237
35. Forstner JF. Intestinal mucins in health and disease. Digestion. (1978) 17: 234-263
36. Fridovich I. Quantitative aspects of the production of superoxide anion radical by milk xanthine oxidase. J Biol Chem. (1970) 245: 4053-4057
37. Garner A, Flemstrom G, Allen A, Heylings JR and McQueen S. Gastric mucosal protective mechanisms: roles of epithelial bicarbonate and mucus secretions. Scand. J. Gastroenterol. (1984) Suppl. 101: 79-86
38. Glavin G.B. and Szabo S. Experimental gastric mucosal injury: laboratory models reveal mechanisms of pathogenesis and new therapeutic strategies. Faseb J (1992) 6: 825-831
39. Goddard PJ, Kao YC and Lichtenberger LM. Luminal surface hydrophobicity of canine gastric mucosa is dependent on a surface mucous gel. Gastroenterology. (1990) 98: 361-370
40. Green T.R., Fellman J.H., Eicher A.L. and Pratt K.L. Antioxidant role and subcellular location of hypotaurine and taurine in human neutrophils. Biochem. Biophys. Acta. (1991) 1073: 91-97
41. Grimble R.F. Nutritional antioxidants and the modulation of inflammation: theory and practice. New Horiz. (1994) 2: 175-185
42. Grisham MB, Von Ritter C, Smith BF, Lamont JT and Granger DN. Interaction between oxygen radicals and gastric mucin. Am. J. Physiol. (1987) 253: G93-G96
43. Guice KS, Oldham KT, Caty MG, Johnson KJ and Ward PA. Neutrophil-dependent, oxygen-radical mediated lung injury associated with acute pancreatitis. Ann Surg. (1989) 210: 740-747
44. Harlan JM. Neutrophil-mediated vascular injury. Acta Med Scand (1987) Suppl. 715: 123-129
45. Halliwell B. Free radicals, antioxidants, and human disease: curiosity, cause, or consequence. Lancet. (1994) 344: 721-724
46. Henriksen EJ and Saengsirisuwan V. Exercise training and antioxidants: relief from oxidative stress and insulin resistance. Exerc. Sport Sci. Rev. (2003) 31: 79-84
47. Hills BA, Butler BD and Lichtenberger LM. Gastric mucosal barrier: hydrophobic lining to the lumen of the stomach. Am. J. Physiol. (1983) 244: 561-568
48. Holzer P, Pabst MA and Lippe I. Intragastric capsaicin protects against aspirin-induced lesion formation and bleeding in the rat gastric mucosa. Gastroenterology (1989) 96: 1425-1433
49. Hoppenkamps R. Thies E. Younes M. Siegers CP. Glutathione and GSH-dependent enzymes in the human gastric mucosa. Klin.Wochenschr. (1984) 62: 183-186
50. Hsu PI, Lin XZ, Chan SH, Lin CY, Chang TT, Shin JS, Hsu LY, Yang CC, Chen KW. Bleeding peptic ulcer-risk factors for rebleeding and sequential changes in endoscopic findings. Gut (1994) 35: 746-749
51. Hung CR and Hwang YY. Role of acid back-diffusion in the formation of mucosal ulceration and its treatment with drugs in diabetic rats. J. Pharm. Pharmacol. (1995) 47: 493-498
52. Hung C.R. and Neu S.L. Acid-induced gastric damage in rats is aggravated by starvation and prevented by several nutrients. J. Nutr. (1997) 127: 630-636
53. Hung C.R. and Hsu, D.Z. Roles of histamine receptors and oxyradicals in aggravation of acid-induced gastric hemorrhagic ulcer in septic rats. Inflammopharmacology (1998) 6: 339-355
54. Hung CR and Wang PS. Role of acid back-diffusion, glutathione, oxyradical, and histamine in antral hemorrhagic ulcer in rats, the protective effect of lysozyme chloride and antioxidants. J. Lab. Clin. Med. (2002) 140: 142-151
55. Kao YC and Lichtenberger LM. Effect of 16,16-dimethyl prostaglandin E2 on lipidic organelles of rat gastric surface mucous cells. Gastroenterology. (1993) 104: 103-113
56. Kato S, Takeuchi K, Okabe S. Mechanism by which histamine increases gastric mucosal blood flow in the rat. Role of luminal H+ .Dig. Dis. Sci (1993) 38: 1224-1232
57. Keller GA, West MA, Cerra FB and Simmons RL. Multiple systems organ failure. Modulation of hepatocyte protein synthesis by endotoxin activated Kupffer cells. Ann Surg. (1985) 201: 87-95
58. Levi M, van der Poll T, ten Cate H and van Deventer SJ. The cytokine-mediated imbalance between coagulant and anticoagulant mechanisms in sepsis and endotoxaemia. Eur J Clin Invest. (1997) 27: 3-9
59. Kingston R., Kelly C.J. and Murray P. The therapeutic role of taurine in ischaemia-reperfusion injury. Cur. Pharm. Design. (2004) 10: 2401-2410
60. Long CL, Nelson KM, Akin JM Jr., Geiger JW, Merrick HW and Blakemore WS. A physiologic basis for the provision of fuel mixtures in normal and stressed patients. J Trauma. (1990) 30: 1077-85; discussion 1085-1086
61. Lorente JA, Garcia-Frade LJ, Landin L, de Pablo R, Torrado C, Renes E and Garcia-Avello A. Time course of hemostatic abnormalities in sepsis and its relation to outcome. Chest. (1993) 103: 1536-1542
62. Lichtenberger LM. The hydrophobic barrier properties of gastrointestinal mucus. Annu. Rev. Physiol. (1995) 57: 565-583
63. Kilbourn RG, Gross SS, Jubran A, Adams J, Griffith OW, Levi R and Lodato RF. NG-methyl-L-arginine inhibits tumor necrosis factor-induced hypotension: implications for the involvement of nitric oxide. Proc Natl Acad Sci U S A. (1990) 87: 3629-3632
64. Lippe IT and Holzer P. Participation of endothelium-derived nitric oxide but not prostacyclin in the gastric mucosal hyperaemia due to acid back-diffusion. Br. J. Pharmacol. (1992) 105: 708-714
65. MacGlashan D Jr. Histamine. A mediator of inflammation. J. Allergy Clin. Immunol. (2003) 112: S53-59
66. Mainous MR, Ertel W, Chaudry IH and Deitch EA. The gut: a cytokine-generating organ in systemic inflammation. Shock. (1995) 4: 193-199
67. Marshall JC, Christou NV, Horn R and Meakins JL. The microbiology of multiple organ failure. The proximal gastrointestinal tract as an occult reservoir of pathogens. Arch Surg. (1988) 123: 309-315
68. Matot I and Sprung CL. Definition of sepsis. Intensive Care Med. (2001) 27 Suppl 1: S3-S9
69. McCuskey RS, Urbaschek R and Urbaschek B. The microcirculation during endotoxemia. Cardiovasc Res. (1996) 32: 752-763
70. Mohn I.K. and Das U.N. Effect of L-arginine-nitric oxide system on chemical-induced diabetes mellitus. Free. Rad. Biol. Med. (1998) 25: 757-765
71. Moore FA. The role of the gastrointestinal tract in postinjury multiple organ failure. Am J Surg. (1999) 178: 449-453
72. Niki T, Oka T, Shiga J and Machinami R. Kupffer cells in multiple organ failure---their activation as revealed by immunohistochemistry for lysozyme, alpha1-antichymotrypsin, and lectins. Gen Diagn Pathol. (1995) 141: 21-27
73. Nishiwake H, Takeuchi K, Okada M, Tanaka H, Okabe S. Stimulation of gastric alkaline secretion by histamine n rats: possible involvement of histamine H2-receptors and endogenous prostaglandins. J Pharmacol Exp Ther (1989) 248: 793-798
74. Ohkawa H, Ohishi N and Yagi K. Assay for lipid peroxides in animal tissues by thiobarbituric acid reaction. Anal. Biochem. (1979) 95: 351-358
75. Olson CE. Glutathione modulates toxic oxygen metabolite injury of canine chief cell monolayers in primary culture. Am. J. Physiol. (1988) 254: G49-G56
76. Perkash I, Satpati P, Agarwal KC, Chakravarti RN and Chhuttani PN. Prolonged peritoneal lavage in fecal peritonitis. Surgery. (1970) 68: 842-845
77. Quinn M.R. Park E. and Schuller-Levis G. Taurine chloramines inhibits prostaglandin E2 production in activated RAW 264.7 cells by post-transcriptional effects on inducible cyclooxygenase expression. Immunol. Lett. (1996) 50: 185-188
78. Raybould HE, Sternini C, Eysselein VE, Yoneda M and Holzer P. Selective ablation of spinal afferent neurons containing CGRP attenuates gastric hyperemic response to acid. Peptides (1992) 13: 249-254
79. Raybould HE. Li DS and Guth PH. Calcitonin gene-related peptide mediates the gastric hyperemic response to acid back-diffusion. Ann. N. Y. Acad. Sci. (1992) 657: 536-537
80. Reiter R.J. Cytoprotective properties of melatonin: presumed association with oxidativedamage and aging. Nutrition (1998) 14: 691-696
81. Ren J, Young RL, Lassiter DC and Harty RF. Calcitonin gene-related peptide mediates capsaicin-induced neuroendocrine responses in rat antrum. Gastroenterology. (1993) 104: 485-491
82. Repka-Ramirez MS. New concepts of histamine receptors and actions. Curr. Allergy Asthma. Rep. (2003) 3: 227-231
83. Ronnberg AL and Hakanson R. A simplified procedure for the fluorometric determination of histamine in rat stomach. Agents Actions. (1984) 14: 195-199
84. Rydning A. Lyng O. Falkmer S. Gronbech JE. Histamine is involved in gastric vasodilation during acid back diffusion via activation of sensory neurons. Am. J. Physiol. (2002) 283: G603-G611
85. Ryu JK, Kim DJ, Lee T, Kang YS, Yoon SM and Suh JK. The role of free radical in the pathogenesis of impotence in streptozotocin-induced diabetic rats. Yonsei Med. J. (2003) 44: 236-241
86. Salim AS. Protection against stress-induced acute gastric mucosal injury by free radical scavengers. Intensive Care Med. (1991) 17: 455-460
87. Saltzman JR and Zawacki JK. Therapy for bleeding peptic ulcers. New Engl J Med. (1997) 336: 1091-1093
88. Shafi MA and Fleischer DE. Risk factors of acute ulcer bleeding. Hepato-Gastroenterol (1999) 6: 727-731
89. Shay H, Komarov SA and Gruenstein M. Effects of vagotomy in the rat. Arch.Surg. (1949) 59: 210-226
90. Shindoh C, Dimarco A, Nethery D and Supinski G. Effect of PEG-superoxide dismutase on the diaphragmatic response to endotoxin. Am Rev Respir Dis. (1992) 145: 1350-1354
91. Stein HJ, Hinder RA and Oosthuizen MM. Gastric mucosal injury caused by hemorrhagic shock and reperfusion: protective role of the antioxidant glutathione. Surgery. (1990) 108: 467-473
92. Supinski G, Nethery D and DiMarco A. Effect of free radical scavengers on endotoxin-induced respiratory muscle dysfunction. Am Rev Respir Dis. (1993) 148: 1318-1324
93. Suttorp N, Toepfer W and Roka L. Antioxidant defense mechanisms of endothelial cells: glutathione redox cycle versus catalase. Am. J. Physiol. (1986) 251: C671-C680
94. Szabo S and Pihan G. Mechanisms of gastric cytoprotection. J Clin Gastronenterol (1987) 9 Suppl 1: 8-13
95. Szabo C, Wu CC, Gross SS, Thiemermann C and Vane JR. Interleukin-1 contributes to the induction of nitric oxide synthase by endotoxin in vivo. Eur J Pharmacol. (1993) 250: 157-160
96. Szelenyi I and Brune K. Possible role of oxygen free radicals in ethanol-induced gastric mucosal damage in rats. Dig. Dis. Sci. (1988) 33: 865-871
97. Takeuchi K, Ueki S, and Okabe S.R. Impotrance of gastric motility in the pathogenesis of indomethacin-induced gastric lesions in rats. Dig. Dis. Sci. (1986) 31: 1114-1122
98. Takeuchi K, Ueshima K, Matsumoto J and Okabe S. Role of capsaicin-sensitive sensory nerves in acid-induced bicarbonate secretion in rat stomach. Dig. Dis. Sci. (1992) 37: 737-743
99. Terashita Z, Imura Y, Nishikawa K and Sumida S. Is platelet activating factor (PAF) a mediator of endotoxin shock? Eur J Pharmacol. (1985) 109: 257-261
100. Vaananen PM. Meddings JB and Wallace JL. Role of oxygen-derivedfree radicals in indomethacin-induced gastric injury. Am. J. Physiol. (1991) 261: G470-G475
101. Vohra, B.P. and Hui, X. Taurine protects against carbon tetrachloride toxicity in the cultured neurons and in vivo. Arch. Physiol. Biochem. (2001) 109: 90-94
102. Walder CE, Thiemermann C and Vane JR. Endothelium-derived relaxing factor participates in the increased blood flow in response to pentagastrin in the rat stomach mucosa. Proc. R. Soc. Lond. B, Biol. Sci. (1990) 241: 195-200
103. Wallace JL and Granger DN. The cellular and molecular basis of gastric mucosal defense. FASEB J. (1996) 10: 731-740
104. Wichterman KA, Baue AE and Chaudry IH. Sepsis and septic shock---a review of laboratory models and a proposal. J Surg Res. (1980) 29: 189-201
105. Worthen GS, Haslett C, Rees AJ, Gumbay RS, Henson JE and Henson PM. Neutrophil-mediated pulmonary vascular injury. Synergistic effect of trace amounts of lipopolysaccharide and neutrophil stimuli on vascular permeability and neutrophil sequestration in the lung. Am Rev Respir Dis. (1987) 136: 19-28
106. Yegen BC. Alican I. Yalcin AS. Oktay S. Calcium channel blockers prevent stress-induced ulcers in rats. Agents Actions. (1992) 35: 130-134
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